1.Focal cerebral ischemia and apoptosis
Chinese Pharmacological Bulletin 1998;0(S1):-
It has been found that apoptosis involves in pathophysiological process of ischemic cerebral injury and plays an important part in neu-ronal injury. To explore the mechanisms of cerebral ischemia and new therapeutic pathways in respect of apoptosis has become the focusing point of neuronal injury research in recent years. This article reviewes recent studies on cerebral ischemia andapoptosis as follows: outline of apoptosis; the presence of an apoptotic component in the loss of neurons following cerebral ischemia; the apoptotic role in process of focal cerebral ischemia; the probable mechanisms of neuronal apoptosis and also unresolved problems in the field.
2.EFFECTS OF DL-3-n-BUTYLPHTHALIDE ON ARACHIDONIC ACID RELEASE AND PHOSPHOLIPASE A2 mRNA EXPRESSION IN CEREBRAL CORTEX AFTER MIDDLE CEREBRAL ARTERY OCCLUSION IN RATS
Acta Pharmaceutica Sinica 2000;35(8):561-565
AIM To study the effect of dl-3-n-butylphthalide (dl-NBP) on arachidonic acid(AA) release and phospholipase A2 (PLA2) mRNA in cerebral cortex of rats subjected to focal cerebral ischemia. METHODS Focal cerebral ischemia was induced by inserting a monofilament nylon suture into the internal carotid artery and blocking the origin of the middle cerebral artery. AA was determined with high performance liquid chromatography (HPLC). The PLA2 mRNA expression was evaluated by Northern blot analysis. RESULTS Six hours of cerebral ischemia induced AA release in the ischemic cerebral cortex. dl-NBP (10 or 20 mg·kg-1) and nimodipine (0.5 mg·kg-1) given intraperitoneally 5 min and 120 min again after the onset of ischemia significantly reduced AA concentration in the cerebral cortex (P<0.01). d-NBP, but not l-NBP, decreased AA release in the brain after middle cerebral artery occlusion. The expression of PLA2 mRNA in cerebral cortex induced by cerebral ischemia was also inhibited by dl-NBP and d-NBP (10 or 20 mg·kg-1, ip). CONCLUSION dl-NBP and d-NBP inhibited AA release and PLA2 mRNA expression in the ischemic brain tissue in vivo.
3.EFFECTS OF 3-N-BUTYLPHTHALIDE ON THROMBOSIS FORMATION AND PLATELET FUNCTION IN RATS
Acta Pharmaceutica Sinica 2001;36(5):329-333
AIM To study the effects of dl-, l- and d-3-n-butylphthalide (NBP) on platelet aggregation and thrombus formation. METHODS Thrombus formation was assessed by silk thread-induced thrombosis in arteriovenous shunt in rats. Rat platelet aggregation induced by adenosine diphosphate (ADP), arachidonic acid (AA), collagen and thrombin was detected in vitro. The generation of thromboxane B2 (TXB2) and the concentration of cAMP in rabbit platelets in vitro were studied with radioimmunological assay. RESULTS dl-, l-NBP (5, 10, 20 mg*kg-1 ip) exhibited a dose-dependent inhibitory effect on thrombus formation in rats, while d-NBP was not active. dl, l, d-NBP (3-100 μmol*L-1) inhibited platelet-rich plasma aggregation in vitro induced by ADP, collagen and AA, and all of them showed no effect on thrombin-induced platelet aggregation. In addition, dl, l-NBP (10-100 μmol*L-1) were found to increase [cAMP]i in dose-related fashion. In the meantime, only high concentration of l-NBP was found to decrease platelet TXA2 level. In addition, l-NBP (1-100 μmol*L-1) showed significant effect on inhibiting 5-HT release from platelets. In contrast, dl- and d-NBP showed no effect. CONCLUSION The results suggest that NBP is a potent antiplatelet drug, the mechanism of its antithrombotic and antiplatelet activity is related to its regulation of cAMP level and 5-HT release.
4.Relationship of up-regulated thrombospondin 1 expression with renal interstitial fibrosis and peritubular capillary loss in chronic aristolochic acid nephropathy
Ying FENG ; Yipu CHEN ; Hong CHENG ; Yanli GAO ; Hongmi DONG ; Zhao HU
Chinese Journal of Nephrology 1994;0(04):-
Objective To investigate the relationship of up-regulated thrombospondin 1 (TSP-1) expression with renal interstitial fibrosis and peritubular capillary loss in chronic aristolochic acid nephropathy(CAAN). Methods Thirty-six male SD rats were randomly divided into two groups, 18 in each one. CAAN rats received 20 mg?kg-1?d-1 aristolochic acid (AA) contained in ethanol extract of Aristolochia manshuriensis Kom by gavage for 5 days in the 1st week, and after a break of 9 days, then 15 mg?kg-1?d-1 AA for 7 days in every other week up to the 12th week. Control group rats (Con) only received tap water by gavage as above. At the end of the 4th, 8th and 12th week, 6 rats in each group were sacrificed. Immunohistochemical staining was performed in rat renal tissue sections to examine the expression of TSP-1, transforming growth factor-?1 (TGF-?1), aminopeptidase P(APP), vascular endothelial growth factor (VEGF) and type I collagen (Col I ). Results Compared with Con, the expression levels of interstitial TSP-1, tubular TGF-P1 and interstitial Col I were all up-regulated in CAAN rats (all P